Clostridium perfringens type C in Neonatal Ruminants: Struck, Lamb Dysentery, and Hemorrhagic Enteritis

Etiology

Clostridium perfringens type C is an anaerobic, Gram-positive, spore-forming bacillus classified within toxinotype C based on its production of alpha toxin (CPA) and beta toxin (CPB). Beta toxin is the principal virulence factor responsible for the enteric and systemic pathology observed in neonatal ruminants. This toxin is a pore-forming protein that inserts into host cell membranes, causing rapid ion flux, osmotic lysis, and necrosis of intestinal epithelial cells and vascular endothelium. The toxin is highly susceptible to proteolytic degradation by trypsin, which explains the age-dependent susceptibility of neonates. Newborn ruminants have low pancreatic trypsin secretion and reduced intestinal trypsin activity, allowing CPB to persist in the gut lumen and exert its cytotoxic effects. [1, 2]

The organism also carries the cpb2 gene encoding beta2 toxin (CPB2) in some isolates, but the role of CPB2 in disease pathogenesis remains uncertain. Songer and Miskimins [1] reported that only 14.3% of bovine isolates from calves with hemorrhagic enteritis were cpb2 positive, and only half of those expressed CPB2. This finding suggests that CPB2 is not a consistent virulence determinant in type C disease, although it may contribute to strain variability.

Clostridium perfringens type C is distinguished from other toxinotypes by the absence of epsilon toxin (ETX) and iota toxin (ITX). The genetic basis for toxin production lies on large plasmids, and horizontal transfer of these plasmids can occur, though type C is a stable toxinotype in field isolates.

Epidemiology

Clostridium perfringens type C is ubiquitous in soil, dust, and the gastrointestinal tract of healthy adult ruminants. Spores are highly resistant to environmental degradation and can persist for years in contaminated premises. Disease occurs sporadically or in outbreaks, primarily in neonatal animals during the first three weeks of life. The three classic syndromes associated with type C infection in neonatal ruminants are struck in lambs, lamb dysentery, and hemorrhagic enteritis in calves and other ruminant neonates.

Struck is a peracute disease of lambs, typically affecting the first week of life. It is characterized by sudden death with minimal clinical signs. Lamb dysentery occurs in lambs up to three weeks of age and presents with acute hemorrhagic diarrhea. Hemorrhagic enteritis in calves is most common in the first few days of life and may involve the abomasum and proximal small intestine. [1]

Risk factors include inadequate colostrum intake, overfeeding of milk or milk replacer, feeding of poorly thawed or contaminated colostrum, and conditions that reduce gut motility. Intensive management systems with high stocking density and poor hygiene predispose to outbreaks. The disease is often seen in well-nourished, fast-growing lambs and calves, suggesting that rapid milk intake and high protein load may overwhelm intestinal proteolytic capacity and allow beta toxin to act. [1, 2]

Clinical Signs

Struck (Lambs)

Struck is a peracute enterotoxemia. Affected lambs are often found dead without premonitory signs. If observed, clinical signs include sudden onset of abdominal pain, distension, recumbency, and bloody diarrhea. The course is rapid, with death occurring within a few hours. Mortality in affected flocks can be high.

Lamb Dysentery

Lamb dysentery presents with acute hemorrhagic diarrhea, tenesmus, dehydration, and depression. Lambs may show reluctance to suckle, weakness, and abdominal pain. The feces are initially pasty and yellow, progressing to bloody and watery. Without intervention, death occurs within 24 to 48 hours. Morbidity and mortality vary but can reach 30% in untreated outbreaks.

Hemorrhagic Enteritis in Calves

In calves, Clostridium perfringens type C causes hemorrhagic enteritis with clinical signs similar to lamb dysentery. Calves develop tympany, abdominal pain, and bloody diarrhea. Songer and Miskimins [1] described a case in a cloned gaur calf that developed pasty yellow and bloody diarrhea, abdominal distension, and died approximately 48 hours after birth despite intensive therapy. The abomasum was distended with clotted milk and bloody fluid, and the abomasal and omasal walls were thickened and hemorrhagic. The proximal duodenum was hemorrhagic and emphysematous.

Pathology

Gross lesions are characteristic and involve the abomasum and small intestine. The abomasum is often distended with clotted milk and bloody fluid, with thickening and hemorrhage of the wall. The small intestine, particularly the duodenum and jejunum, shows segmental hemorrhagic enteritis with mucosal congestion, edema, and necrosis. The intestinal lumen may contain bloody fluid. Emphysema of the intestinal wall is occasionally observed. [1]

Histopathology reveals acute, necrotizing, hemorrhagic inflammation of the mucosa and submucosa. Gram-positive rods are abundant on the mucosal surface and within the submucosa. Beta toxin causes vascular necrosis and thrombosis, leading to ischemic necrosis of villi. The lamina propria is infiltrated with neutrophils and erythrocytes. In chronic cases, a diphtheritic membrane may form.

Diagnostics

Definitive diagnosis requires laboratory confirmation of Clostridium perfringens type C and its toxins. A diagnostic algorithm is presented in the Mermaid diagram below.

Sample Collection

Samples should include intestinal contents (from the small intestine), feces, and affected tissue (abomasum, intestine). Samples must be collected as soon as possible after death and transported under anaerobic conditions or refrigerated.

Laboratory Methods

• Gram stain: Smears from intestinal mucosa or contents reveal numerous Gram-positive rods, often in chains.
• Anaerobic culture: Isolation on blood agar and egg yolk agar (for lecithinase activity) under anaerobic conditions. Colonies show a double zone of hemolysis on blood agar.
• Toxinotyping PCR: Multiplex PCR targeting cpa (alpha toxin), cpb (beta toxin), etx (epsilon toxin), iap (iota toxin), and cpb2 (beta2 toxin). Detection of cpa and cpb confirms type C.
• ELISA: Commercial ELISA kits for beta toxin detection in intestinal contents provide rapid confirmation.
• Histopathology: Hematoxylin and eosin and Gram stains of formalin-fixed tissue show characteristic necrotizing hemorrhagic enteritis with Gram-positive rods.

Differential Diagnoses

Differential diagnoses include other clostridial enteritides (type A, type D), coccidiosis, cryptosporidiosis, salmonellosis, bovine viral diarrhea, and enterotoxigenic Escherichia coli. [1, 2]

flowchart TD
    A[Neonatal Ruminant with Acute Diarrhea or Sudden Death], > B{Clinical Signs}
    B, > C[Peracute death, abdominal distension, bloody diarrhea]
    C, > D[Suspect Clostridium perfringens type C]
    D, > E[Collect Samples: intestinal contents, feces, tissue]
    E, > F[Gram Stain: Gram-positive rods]
    E, > G[Anaerobic Culture]
    E, > H[PCR for Toxin Genes: cpa, cpb]
    E, > I[ELISA for Beta Toxin]
    F, > J[Confirmatory Diagnosis]
    G, > J
    H, > J
    I, > J
    J, > K[Treatment: Antitoxin, Antibiotics, Supportive Care]
    J, > L[Control: Vaccination, Colostrum Management, Hygiene]

Treatment

Treatment is often unsuccessful due to the peracute nature of the disease. Early intervention may improve survival. Therapeutic options include:

• Antitoxin: Polyvalent clostridial antitoxin containing antibodies against beta toxin can be administered subcutaneously or intravenously if given early in the course of disease.
• Antimicrobials: Penicillin (procaine penicillin G or amoxicillin) or metronidazole are effective against Clostridium perfringens. Antimicrobial therapy should be initiated promptly.
• Supportive care: Fluid therapy with isotonic crystalloids to correct dehydration and electrolyte imbalances. Nonsteroidal anti-inflammatory drugs may be used for pain and inflammation.
• Intestinal protectants: Bismuth subsalicylate or kaolin-pectin may be used adjunctively.

In outbreaks, treatment of in-contact animals with antitoxin and antimicrobials may reduce mortality.

Control

Control of Clostridium perfringens type C disease relies on vaccination and management.

Vaccination

Pregnant dams should be vaccinated with multivalent clostridial vaccines containing type C toxoid. Vaccination is typically given 4 to 6 weeks before parturition, with a booster 2 to 3 weeks later. This ensures high levels of maternal antibodies in colostrum. Neonates acquire passive immunity through colostrum intake within the first 12 to 24 hours of life. Vaccination programs should be tailored to the specific risk in each herd or flock.

Management Practices

• Ensure adequate colostrum intake: All neonates should receive sufficient colostrum from vaccinated dams within the first few hours of life.
• Avoid overfeeding: Limit milk or milk replacer volume per feeding to prevent intestinal overload.
• Maintain hygiene: Clean and disinfect calving and lambing areas. Remove contaminated bedding.
• Isolate affected animals: Separate sick neonates from healthy ones to reduce environmental contamination.
• Sporicidal disinfection: Clostridium perfringens spores are resistant to many disinfectants. Use sporicidal agents such as 10% bleach or peracetic acid for contaminated surfaces.

Outbreak Management

During an outbreak, all neonates should receive antitoxin and antimicrobial prophylaxis. Vaccination of the dam herd should be reviewed and updated. Environmental decontamination is critical to prevent recurrence.

Cross-References

For comparison with other clostridial diseases, see Clostridium perfringens Type A in Broilers: Necrotic Enteritis Diagnosis and Alternatives to Antibiotics and Clostridium perfringens Type D: Pulpy Kidney Disease (Enterotoxemia) in Sheep – Pathogenesis and Control. For other clostridial infections in ruminants, see Clostridium chauvoei: Blackleg in Cattle and Clostridium novyi: Black Disease in Sheep. For neonatal enteric diseases, see Cryptosporidiosis in Neonatal Ruminants: Molecular Diagnostics and Zoonotic Strain Surveillance.

References

[1] Songer JG, Miskimins D. Clostridial abomasitis in calves: Case report and review of the literature. Anaerobe. 2005. URL: https://www.semanticscholar.org/paper/a7e1ad2176adbcd85c86cbb6733a0b4eceb2cc27

[2] Gülçubuk A. Clostridial infections and malign edema in farm animals. Journal. 2020. URL: https://www.semanticscholar.org/paper/96989414517bab26c54b45eed895fe7de07755fe